Normal Anatomy and Neurophysiology of the Hippocampal Formation

Knowles, W. Douglas

doi:10.1097/00004691-199204010-00006

Cited by 74 publications

(56 citation statements)

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“…The hippocampus and entorhinal cortex play major roles in learning and memory (Knowles et al, 1992;Alvarez et al, 1995;Bannerman et al, 2001;Buckmaster et al, 2004). Also, they are primary sites for β-amyloid deposition in APP transgenic mice (Su and Ni, 1998;Reilly et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Spatial relationship between synapse loss and β‐amyloid deposition in Tg2576 mice

Dong

Martin

Chambers

et al. 2006

J of Comparative Neurology

131

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Although there is evidence that β-amyloid impairs synaptic function, the relationship between β-amyloid and synapse loss is not well understood. In this study, we assessed synapse density within the hippocampus and the entorhinal cortex of Tg2576 mice at 6-18 months of age using stereological methods at both the light and electron microscope levels. Under light microscopy, we failed to find overall decreases in the density of synaptophysin-positive boutons in any brain areas selected, but bouton density was significantly decreased within 200 μm of compact β-amyloid plaques in the outer molecular layer of the dentate gyrus and layers II and III of the entorhinal cortex at 15-18 months of age in Tg 2576 mice. Under electron microscopy, we found overall decreases in synapse density in the outer molecular layer of the dentate gyrus at both 6-9 and 15-18 months of age, and in layers II and III of the entorhinal cortex at 15-18 months of age in Tg 2576 mice. However, we did not find overall changes in synapse density in the stratum radiatum of the CA1 subfield. Furthermore, in the two former brain areas, we found a correlation between lower synapse density and greater proximity to β-amyloid plaques. These results provide the first quantitative morphological evidence at the ultrastructure level of a spatial relationship between β-amyloid plaques and synapse loss within the hippocampus and the entorhinal cortex of Tg2576 mice.

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Section: Discussionmentioning

confidence: 99%

Spatial relationship between synapse loss and β‐amyloid deposition in Tg2576 mice

Dong

Martin

Chambers

et al. 2006

J of Comparative Neurology

131

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“…BNPI mRNA appears to be expressed exclusively in discrete populations of neurons in rat brain (Ni et al, 1994. Prominent BNPI RNA expression is found in several regions of the brain that have concentrated perikarya of presumed glutamatergic neurons, such as cerebral cortical layers II-VI, the pyramidal cell layer of the hippocampus, the granule cell layers of the dentate gyrus and the cerebellum, the entorhinal cortex, and the piriform cortex (Storm-Mathisen and Ottersen, 1986;Knowles, 1992;Conti and Minelli, 1994). The general expression pattern of BNPI is suggestive of a preferential localization in glutamatergic neurons.…”

Section: Eat-4 Is Involved Specifically In the Synaptic Function Of Gmentioning

confidence: 99%

EAT-4, a Homolog of a Mammalian Sodium-Dependent Inorganic Phosphate Cotransporter, Is Necessary for Glutamatergic Neurotransmission inCaenorhabditis elegans

et al. 1999

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The Caenorhabditis elegans gene eat-4 affects multiple glutamatergic neurotransmission pathways. We find that eat-4 encodes a protein similar in sequence to a mammalian brainspecific sodium-dependent inorganic phosphate cotransporter I (BNPI). Like BNPI in the rat CNS, eat-4 is expressed predominantly in a specific subset of neurons, including several proposed to be glutamatergic. Loss-of-function mutations in eat-4 cause defective glutamatergic chemical transmission but appear to have little effect on other functions of neurons. Our data suggest that phosphate ions imported into glutamatergic neurons through transporters such as EAT-4 and BNPI are required specifically for glutamatergic neurotransmission.

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“…We focused our structural assessments on the hippocampal formation because these structures play a major role in learning and memory (Knowles, 1992;Bannerman et al, 2001) and is also a site for Ab deposition in AD patients (Probst et al, 1983;West et al, 2004) and in several transgenic mouse models of AD (Su and Ni, 1998;Reilly et al, 2003). Synapse loss induced by Ab remains a likely basis for the behavioral deficits observed in Tg2576 mice (Stern et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Dong

Yuede

Coughlan

et al. 2008

Neuropsychopharmacol

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Memantine, an uncompetitive NMDA receptor antagonist used for the treatment of Alzheimer's disease (AD), has been hypothesized to have neuroprotective properties. However, the similarity of its mechanism of action to other NMDA receptor antagonists has led to concerns that it may also have neurotoxic effects. To assess both the neuroprotective and neurotoxic potential of memantine in a mouse model of AD (Tg2576 mice), we used quantitative light and electron microscopy to investigate the effects of long-term (6 months) administration of memantine (5, 10 and 20 mg/kg) on plaque deposition and neuronal morphology in the hippocampus and overlying cortex. A fear-conditioning paradigm was used to evaluate the behavioral consequences of any observed changes in structure. Administration of the two higher doses of memantine (10 and 20 mg/kg) was associated with a significant decrease in b-amyloid (Ab) plaque deposition, increases in synaptic density and the appearance of degenerating axons; the latter two effects were independent of genotype. Administration of the lowest dose of memantine (5 mg/kg) was associated with a significant decrease in Ab plaque deposition and a significant increase in synaptic density, but not a significant increase in degenerating axons. However, memantine did not significantly improve behavioral deficits associated with genotype in a fear-conditioning paradigm at any dose. These results suggest that chronic memantine administration may have both neuroprotective and neurotoxic effects in a mouse model of AD.

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Normal Anatomy and Neurophysiology of the Hippocampal Formation

Cited by 74 publications

References 0 publications

Spatial relationship between synapse loss and β‐amyloid deposition in Tg2576 mice

Spatial relationship between synapse loss and β‐amyloid deposition in Tg2576 mice

EAT-4, a Homolog of a Mammalian Sodium-Dependent Inorganic Phosphate Cotransporter, Is Necessary for Glutamatergic Neurotransmission inCaenorhabditis elegans

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

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